The genetic background of the European Mesolithic and the extent of population replacement during the Neolithic [1,2,3,4,5,6,7,8,9,10] is poorly understood, both due to the scarcity of human remains from that period [11,12,13,14,15,16,17,18] and the inherent methodological difficulties of ancient DNA research. However, advances in sequencing technologies are both increasing data yields and providing supporting evidence for data authenticity, such as nucleotide misincorporation patterns [19,20,21,22]. We use these methods to characterize both the mitochondrial DNA genome and generate shotgun genomic data from two exceptionally well-preserved 7,000-year-old Mesolithic individuals from La Braña-Arintero site in León (Northwestern Spain) [23]. The mitochondria of both individuals are assigned to U5b2c1, a haplotype common among the small number of other previously studied Mesolithic individuals from Northern and Central Europe. This suggests a remarkable genetic uniformity and little phylogeographic structure over a large geographic area of the pre-Neolithic populations. Using Approximate Bayesian Computation, a model of genetic continuity from Mesolithic to Neolithic populations is poorly supported. Furthermore, analyses of 1.34% and 0.53% of their nuclear genomes, containing about 50,000 and 20,000 ancestry informative SNPs, respectively, show that these two Mesolithic individuals are not related to current populations from either the Iberian Peninsula or Southern Europe.

A worldwide genomic principal component analysis (PCA) with data from the 1000 Genomes Project [31] places La Braña 1 and 2 near, but not within the variation of current European populations (Figure S2). However, when compared exclusively to European populations, La Braña 1 and 2 fall closer to Northern European populations such as CEU and Great Britons than Southern European groups such as Iberians or Tuscans (Figure 3). With 1KGPomni chip [31] data, the PCA generates a similar pattern (Figure S3), although the general geographic structure is less clear because of the limited number of SNPs (see Supplemental Experimental Procedures).

2. Modern Europeans are unlike those two ancient remains because they were not among our ancestors and did not share any common ancestor with us who was reasonably close to them?

This is completely against one of the arguments of the study, which proposes based on mt-DNA U5b a Mesolithic substratum extending all over Europe.

Quote from: Sanchez.Quinto.et.al.2012

The mitochondria of both individuals are assigned to U5b2c1, a haplotype common among the small number of other previously studied Mesolithic individuals from Northern and Central Europe. This suggests a remarkable genetic uniformity and little phylogeographic structure over a large geographic area of the pre-Neolithic populations.

Of course, it is very likely that there was some population structure amongst European Mesolithics, and any uniformity conclusions based upon two individuals is far from conclusive. Moreover, the further back in time our TMRCA goes with respect to these two individuals, the closer their position to East Asians, or Sub-Saharan Africans would be on a global PCA map. Mainly because it is known that we share common ancestry with East Asians in a time frame of 20,000-50,000 ybp, the closer our TMRCA with these two HG gets to that date, the closer they would show in a PCA plot to East Asians. Of course, they will never plot with East Asians, because the genome of East Asians has undergone drift and selection since the separation from West Asians/Europeans, which is obvious in any PCA graph. Their global positioning just outside of the European cluster in a PCA map suggest that our TMRCA is indeed very recent, likely dating to the Mesolithic. There are different kinds of genetic drift, but since drift is random, one could argue that the observed trend is the product of natural selection and drift. After all, the PCA were done with 20,000 SNPs(Single Nucleotide Polymorphism), meaning they did not compare chuncks of DNA, but specific points of the DNA where a mutation has occured, which makes modern Europeans different from Asians or Africans. So it is very likely that a small percentage of those mutations occured in the post-7000 ybp period in Europeans, so in a sense these two Mesolithic skeletons retain the ancestral allele value, which in turn, unless it has also mutated in Africans, or Asians, it would be the same. This is the effect that is causing the slight deviation observed in the global PCA graph.

Also when given the choice of only European populations in a PCA analysis, these individuals plot right next to the NW Europeans, why don’t the cluster east of the Finns, or South of the Spaniards, or on the Southeast corner, since their outlier status in the European variation should manifest itself regardless of whether they are plot on a European or Worldwide PCA. After all, don’t Swedish Hunter Gatherers plot “East” of Russians and Finns, even in a European only PCA, thus showing that they had higher Eastern affinities than both, and that even in an intra-European plot they would still appear to be slightly outside of the European variation.

I see no reasoning behind it, other than overthinking the meaning of some of the ADMIXTURE components, which after all, were created using modern populations.

Whatever components the Hunter Gatherers had were akin to Mesolithic Europeans, they might not harbor Mesolithic alleles in its entirety, but at least partially(As in the SNPS that intersect with the HG SNPs) they do.

For the (partial) continuity argument to work, brana would need to be essentially full meso European. Otherwise, the closer relationship brana has to western Europeans could be due to that "other" element.

For the (partial) continuity argument to work, brana would need to be essentially full meso European. Otherwise, the closer relationship brana has to western Europeans could be due to that "other" element.

Any skepticism for the components found in the La Braña samples as being Mesolithic or not, should in fact arise from the dating being borderline(7000 ybp there are already Neolithic sites in Avellaner, Catalonia which turned out to be G2a and E-V13 in Y-DNA Haplogroups) with the Neolithic ages in Iberia, and the burial context not fitting with the observed funerary practices of Mesolithic Europeans(i.e. That the bodies were found in the cave, but were not interred in the ground like every other Mesolithic burial). Now, if we are to accept that the La Braña samples are Mesolithic Europeans, then any component found in them, at least in the SNPs typed, should be considered as Mesolithic European, if a component is labeled Neolithic farmer, and it shows up in the Mesolithic samples, then it means that part of that component labeled Neolithic farmer was in fact present in pre-Neolithic Hunter-Gatherers.

A worldwide genomic principal component analysis (PCA) with data from the 1000 Genomes Project [31] places La Braña 1 and 2 near, but not within the variation of current European populations (Figure S2). However, when compared exclusively to European populations, La Braña 1 and 2 fall closer to Northern European populations such as CEU and Great Britons than Southern European groups such as Iberians or Tuscans (Figure 3). With 1KGPomni chip [31] data, the PCA generates a similar pattern (Figure S3), although the general geographic structure is less clear because of the limited number of SNPs (see Supplemental Experimental Procedures).

2. Modern Europeans are unlike those two ancient remains because they were not among our ancestors and did not share any common ancestor with us who was reasonably close to them?

This is completely against one of the arguments of the study, which proposes based on mt-DNA U5b a Mesolithic substratum extending all over Europe.

Quote from: Sanchez.Quinto.et.al.2012

The mitochondria of both individuals are assigned to U5b2c1, a haplotype common among the small number of other previously studied Mesolithic individuals from Northern and Central Europe. This suggests a remarkable genetic uniformity and little phylogeographic structure over a large geographic area of the pre-Neolithic populations.

Of course, it is very likely that there was some population structure amongst European Mesolithics, and any uniformity conclusions based upon two individuals is far from conclusive. Moreover, the further back in time our TMRCA goes with respect to these two individuals, the closer their position to East Asians, or Sub-Saharan Africans would be on a global PCA map. Mainly because it is known that we share common ancestry with East Asians in a time frame of 20,000-50,000 ybp, the closer our TMRCA with these two HG gets to that date, the closer they would show in a PCA plot to East Asians. Of course, they will never plot with East Asians, because the genome of East Asians has undergone drift and selection since the separation from West Asians/Europeans, which is obvious in any PCA graph. Their global positioning just outside of the European cluster in a PCA map suggest that our TMRCA is indeed very recent, likely dating to the Mesolithic. There are different kinds of genetic drift, but since drift is random, one could argue that the observed trend is the product of natural selection and drift. After all, the PCA were done with 20,000 SNPs(Single Nucleotide Polymorphism), meaning they did not compare chuncks of DNA, but specific points of the DNA where a mutation has occured, which makes modern Europeans different from Asians or Africans. So it is very likely that a small percentage of those mutations occured in the post-7000 ybp period in Europeans, so in a sense these two Mesolithic skeletons retain the ancestral allele value, which in turn, unless it has also mutated in Africans, or Asians, it would be the same. This is the effect that is causing the slight deviation observed in the global PCA graph.

Also when given the choice of only European populations in a PCA analysis, these individuals plot right next to the NW Europeans, why don’t the cluster east of the Finns, or South of the Spaniards, or on the Southeast corner, since their outlier status in the European variation should manifest itself regardless of whether they are plot on a European or Worldwide PCA. After all, don’t Swedish Hunter Gatherers plot “East” of Russians and Finns, even in a European only PCA, thus showing that they had higher Eastern affinities than both, and that even in an intra-European plot they would still appear to be slightly outside of the European variation.

These are the hihlights!Highlights► The first complete Mesolithic mtDNA genome retrieved ► There is a remarkable genetic uniformity in Europe during the Mesolithic period ► Modern Iberians are not direct descendants of the 7,000-year-old hunter-gatherers ► Genetic discontinuity between Mesolithic/Neolithic populations supported by simulations

These are the hihlights!Highlights► The first complete Mesolithic mtDNA genome retrieved ► There is a remarkable genetic uniformity in Europe during the Mesolithic period ► Modern Iberians are not direct descendants of the 7,000-year-old hunter-gatherers ► Genetic discontinuity between Mesolithic/Neolithic populations supported by simulations

You obviously must write to them and correct them of their error!

No need to do that, I have already analyzed the study extensively here. As for the highlights, some of the stuff can indeed be corrected, however, I doubt the authors would do anything about it. For example:

First complete Mesolithic mtDNA genome retrieved.

Is indeed correct, so no need to say anything about it.

There is a remarkable genetic uniformity in Europe during the Mesolithic period.

The uniformity is only based on mt-DNA haplogroup U, so in a sense it is genetic uniformity, but the average reader would interpret that as autosomal uniformity, which is something that remains unknown. Also, such statement completely ignores the presence of mt-DNA H in Magdalenian Cantabria, or Mesolithic Guipuzcoa, but that is another story.

Modern Iberians are not direct descendants of the 7,000-year-old hunter-gatherers.

Well, that is a bit of generalization, as it assumes that every single hunter-gatherer living in Iberia, and Europe at the time was very similar genetically to these two fellows. Also, notice they say that Modern Iberians are not direct descendants, that doesn’t exclude partial ancestry though.